National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Denmark.
Contact Dermatitis. 2011 Sep;65 Suppl 1:1-68. doi: 10.1111/j.1600-0536.2011.01957.x.
Over the 20th century, the frequent use of nickel in consumer products resulted in an increasing prevalence of nickel allergy. Risk items included suspenders in the 1950s-1960s; buttons, zippers and rivets in the 1970s; and ear-piercing jewellery in the 1980s. When subjects allergic to nickel were exposed to nickel in high concentrations, it often resulted in allergic nickel contact dermatitis and hand eczema. In 1990, the Danish government began to regulate consumer nickel exposure as a response to the increasing nickel allergy problem. In 1994, the EU Nickel Directive was passed, a regulation that was based on the Danish and Swedish nickel regulations. These major public health interventions were expected to change the epidemiology of nickel allergy and dermatitis in Europe. Furthermore, it was debated whether nickel would be replaced by cobalt in inexpensive jewellery and result in higher prevalence of cobalt allergy. An evaluation of the possible effects of the European nickel regulations is of importance to ensure protection of consumers and dermatitis patients. This doctoral thesis aimed to evaluate the effects of regulatory interventions on nickel exposure by investigating the development of nickel allergy and dermatitis before and after nickel regulation. Furthermore, a change in the association between nickel allergy and hand eczema was evaluated. The nickel spot test was validated to determine its value when used for screening purposes. Possible explanations for the persistence of nickel allergy were explored including genetic predisposition and consumer nickel exposure from jewellery and accessories. A cobalt spot test was developed and validated. Finally, it was evaluated whether a cobalt allergy epidemic had replaced the nickel allergy epidemic after nickel regulation in terms of increasing cobalt sensitization and cobalt exposure. The thesis showed that the prevalence of nickel allergy decreased significantly after nickel regulation in young Danish women from the general population (18-35 years) and in young Danish female dermatitis patients from a university patch test clinic (0-30 years). Stratification by ear-piercing status revealed that women ear pierced before 1990 had a significantly higher prevalence of nickel allergy and dermatitis than women ear pierced after 1990. Furthermore, the association between hand eczema and nickel allergy decreased in young women aged 18-35 years when a comparison was made between women who were patch tested and questioned in, respectively, 1990 and 2006. Despite the decreasing prevalence of nickel allergy, this condition remains prevalent in young Danish women, as about 10% are nickel allergic. Genetic predisposition to nickel allergy was evaluated by investigating the possible association between filaggrin null mutation status and nickel allergy. A positive association was found but it was also concluded that environmental nickel exposure is of much greater importance. Thus, of 354 consumer items purchased from 36 different stores in Copenhagen, 22% released nickel in concentrations that may result in nickel dermatitis in sensitized subjects. Therefore excessive consumer nickel exposure remains common in Denmark and may be an important explanation for the persistence of nickel allergy. Excessive nickel release was also frequent when samples of earrings purchased in Warsaw and London were examined with the nickel spot test, in particular earrings purchased from street markets and shops with independent ownership. Only very weak indications of an emerging cobalt allergy epidemic were found, as the prevalence of cobalt allergy has not yet increased in young people and only four of 354 consumer items purchased in Copenhagen released cobalt in concentrations that may result in cobalt dermatitis in sensitized individuals. The specificity of the nickel spot test was 98% and the sensitivity 59%. Also, a cobalt spot test was developed and validated and seemed to be a useful diagnostic tool. In conclusion, the Danish nickel regulation and the EU Nickel Directive have changed the epidemiology of nickel allergy in Denmark. However, the Nickel Directive and its reference methods need to be revised to better protect consumers and dermatitis patients.
在 20 世纪，镍在消费品中的频繁使用导致镍过敏的患病率增加。风险物品包括 20 世纪 50 年代至 60 年代的吊带；70 年代的纽扣、拉链和铆钉；以及 80 年代的耳环。当对镍过敏的受试者暴露于高浓度的镍时，通常会导致过敏性镍接触性皮炎和手部湿疹。1990 年，丹麦政府开始规范消费者对镍的暴露，以应对日益严重的镍过敏问题。1994 年，欧盟镍指令通过，该指令是基于丹麦和瑞典的镍法规。这些主要的公共卫生干预措施预计将改变欧洲镍过敏和皮炎的流行病学。此外，人们还争论镍是否会被廉价珠宝中的钴取代，并导致钴过敏的患病率增加。评估欧洲镍法规的可能影响对于确保消费者和皮炎患者的保护至关重要。本博士论文旨在通过研究镍监管前后镍过敏和皮炎的发展情况，评估监管干预对镍暴露的影响。此外，还评估了镍过敏与手部湿疹之间的关联是否发生变化。镍斑贴试验得到了验证，以确定其在筛查目的中的价值。还探讨了镍过敏持续存在的可能原因，包括遗传易感性和珠宝及配饰带来的消费者镍暴露。开发并验证了钴斑贴试验。最后，评估了镍监管后，钴过敏是否会取代镍过敏，出现钴过敏流行，从而导致钴致敏和钴暴露增加。本论文表明，在丹麦普通人群（18-35 岁）和丹麦年轻女性皮炎患者（0-30 岁）中，镍过敏的患病率在镍监管后显著下降。分层分析穿孔状况表明，1990 年前穿孔的女性与 1990 年后穿孔的女性相比，镍过敏和皮炎的患病率明显更高。此外，在 1990 年和 2006 年分别进行斑贴试验和询问的年轻女性（18-35 岁）之间进行比较时，手部湿疹与镍过敏之间的关联减少。尽管镍过敏的患病率下降，但这种情况在丹麦年轻女性中仍然很常见，因为约有 10%的女性对镍过敏。通过研究可能与丝聚蛋白缺失突变状态相关的镍过敏的关联，评估了镍过敏的遗传易感性。发现了阳性关联，但也得出结论，环境镍暴露更为重要。因此，在哥本哈根的 36 家不同商店购买的 354 件消费品中，有 22%的产品释放出的镍浓度可能导致致敏受试者出现镍皮炎。因此，丹麦仍然存在过度的消费者镍暴露，这可能是镍过敏持续存在的一个重要解释。在使用镍斑贴试验检查从华沙和伦敦购买的耳环样本时，也发现了过度的镍释放，尤其是从街头市场和独立经营的商店购买的耳环。仅发现了钴过敏流行的微弱迹象，因为年轻人的钴过敏患病率尚未增加，并且在哥本哈根购买的 354 件消费品中只有 4 件释放出的钴浓度可能导致致敏个体出现钴皮炎。镍斑贴试验的特异性为 98%，敏感性为 59%。此外，还开发并验证了一种钴斑贴试验，似乎是一种有用的诊断工具。总之，丹麦的镍法规和欧盟的镍指令改变了丹麦的镍过敏流行病学。然而，镍指令及其参考方法需要修订，以更好地保护消费者和皮炎患者。
